Journal of Alzheimer’s Disease 88 (2022) 1263–1278 1263

DOI 10.3233/JAD-220243
IOS Press

Systematic Review

Exercise Training for Mild Cognitive

Impairment Adults Older Than 60:
A Systematic Review and Meta-Analysis
Hui Lia,b,c , Wenlong Sub , Hui Danga,b,c , Kaiyue Hanb , Haitao Lub ,
Shouwei Yuea,c,∗ and Hao Zhanga,b,c,∗
a Rehabilitation Center, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong,
China
b China Rehabilitation Research Center, Beijing, China
c University of Health and Rehabilitation Sciences, Qingdao, Shandong, China

Handling Associate Editor: Jianping Jia

Accepted 31 May 2022

Pre-press 2 July 2022

Abstract.
Background: The prevalence of mild cognitive impairment (MCI) continues to increase due to population aging. Exercise
has been a supporting health strategy that may elicit beneficial effects on cognitive function and prevent dementia.
Objective: This study aimed to examine the effects of aerobic, resistance, and multimodal exercise training on cognition in
adults aged > 60 years with MCI.
Methods: We searched the Cochrane Library, PubMed, and Embase databases and ClinicalTrials.gov (https://clinicaltrials.
gov) up to November 2021, with no language restrictions. We included all published randomized controlled trials (RCTs)
comparing the effect of exercise programs on cognitive function with any other active intervention or no intervention in
participants with MCI aged > 60 years.
Results: Twelve RCTs were included in this review. Meta-analysis results revealed significant improvements in resistance
training on measures of executive function (p < 0.05) and attention (p < 0.05); no significant differences were observed between
aerobic exercise and controls on any of the cognitive comparisons.
Conclusion: Exercise training had a small beneficial effect on executive function and attention in older adults with MCI.
Larger studies are required to examine the effects of exercise and the possible moderators.

Keywords: Aged, exercise, meta-analysis, mild cognitive impairment, systematic review

INTRODUCTION

Alzheimer’s disease (AD) is a neurodegenerative

∗ Corresponding
disorder that is the most common cause of demen-
authors: Prof. Shouwei Yue and Prof. Hao
Zhang, Department of Rehabilitation, Qilu Hospital, Shandong
tia [1]. In the initial stage of AD, the decline in
University, Jinan, Shandong, China. Tel.: +86 010 87569345; cognitive function can be significantly subtle and is
E-mails: shouweiy@sdu.edu.cn; crrczh2020@163.com. currently being clinically identified as degenerative

ISSN 1387-2877 © 2022 – The authors. Published by IOS Press. This is an Open Access article distributed under the terms
of the Creative Commons Attribution License (CC BY 4.0).
1264 H. Li et al. / Review of Exercise Treatment on MCI
mild cognitive impairment (MCI) [2]. There are
three clinical subtypes of MCI: amnestic MCI, MCI
involving various degrees of impairment in multi-
ple cognitive domains, and MCI involving a single
non-memory domain. Patients with MCI normally
have self- or informant-reported cognitive complaints
[3] and documented objective impairment in one or
more cognitive domains that is greater than would be
expected for the patient’s age or educational back-
ground [4], but still preserved the activities of daily
living without significant impairment in social or
occupational functions [5]. The prevalence of MCI
increases with age (6.7% for ages 60–64 years, 65.2%
in older adults aged > 60 years), and patients with
MCI are at a higher risk of progressing to dementia
than age-matched controls (progression to dementia
at a rate of approximately 14.9% in MCI aged > 65
years followed by 2 years) [6]. To date, there is no
pharmacologic management currently approved for
MCI, and behavioral training, such as cognitive ther-
apy and exercise training, has symptomatic cognitive
benefits in MCI [7–9].
Considering the feasibility and acceptability of
intervention training, exercise seems to be an avail-
able and economical therapeutic intervention for
individuals at an earlier point of cognitive decline.
Evidence indicates that exercise elicits cognition-
and neurovascular oxygenation-promoting effects in
rodents by reducing amyloid pathology [10–12];
enhancing hippocampal neurogenesis [13], oxidative
stress [14–16], and intracranial energy metabolism
[17]; and reducing neuroinflammation [18]. How-
ever, findings are mixed in human studies. Evidence
suggests that exercise reduces vascular risk factors,
such as hypertension [19], dyslipidemia [20], type 2
diabetes [21], obesity [22], subclinical atherosclero-
sis [23], and arrhythmias [24], which are associated
with a greater risk of cognitive impairment and
dementia [25]. Moreover, exercise may reduces the
risk of stroke [26]. Recent meta-analyses showed
that physical exercise may help preserve or even
improve cognitive function [27–29] and periph-
eral brain-derived neurotrophic factor concentrations
[30, 31] in healthy older adults. Exercise increases
precentral cortical thickness and reduces neuroplas-
ticity [32]; augments gray and white matter volumes
[33], hippocampal volume [34–36], and systemic
levels of glycosylphosphatidylinositol-specific phos-
pholipase; and ameliorates age-related regenerative
impairments [37].
Previous studies have reported a valid effect of
exercise training on cognitive function in older adults
with and without cognitive impairment [38–40] with
a general effect of exercise training [41–43]. For
instance, all levels of physical activity were reported
to have a significant and consistent protective effects
against the occurrence of cognitive decline [44]. Nev-
ertheless, studies on the effects of physical exercise
in older adults with MCI are insufficient and vary in
efficacy owing to the large variability in exercise pro-
tocols, compliance, and complicated interpretation of
the results [43]. This review involved patients with
MCI aged > 60 years, when the global prevalence
rates of dementia are exacerbated continuously. We
compared the results with previous reviews by exam-
ining the effects of aerobic, resistance, mind–body,
and multimodal exercise training on cognitive per-
formance in patients with MCI. These results may
be helpful in clarifying the efficacy of exercise inter-
ventions on cognitive function in older adults with
MCI.
MATERIALS AND METHODS
This study was conducted according to the Pre-
ferred Reporting Items for Systematic Reviews and
Meta-Analysis. The study protocol was registered
with the International Prospective Register of Sys-
tematic Reviews (CRD42021259555).
Search strategy
A librarian-led systematic search of Embase,
PubMed, and Cochrane databases was performed
using a strategy combining selected Medical Sub-
ject Headings terms (exercise, exercise therapy,
resistance training, sports, physical fitness, circuit-
based exercise, endurance training, Tai Ji, bicycling,
yoga, walking, jogging, running, swimming, muscle
stretching exercises, plyometric exercise, cognitive
dysfunction, aged) and free-text terms (For full
search strategy, see the Supplementary Material).
No language or other limitations were imposed dur-
ing the search process. Additionally, we searched
ClinicalTrial.gov, reference lists of selected articles,
and related review articles to screen for related
clinical trials being conducted. The search terms
regarding random control study design (randomized
controlled trial [Publication Type] OR randomized
[Title/Abstract] OR placebo [Title/Abstract]) were
obtained from McMaster University Health Infor-
mation’s website. The last search was performed on
November 5, 2021.
 H. Li et al. / Review of Exercise Treatment on MCI
Criteria for considering studies for this review
Types of studies
Human subject studies designed as randomized
controlled trial (RCT) published in English were
included without year restriction. Nonrandomized
controlled studies, conference abstracts, reviews, pro-
tocols, and secondary analyses were excluded.
Types of participants
Participants diagnosed with MCI according to
accepted criteria (Petersen, Winblad, Morris, Albert
criteria) and aged > 60 years were included. We
excluded healthy aging elderly adults, patients with
any form of dementia, or those diagnosed with cog-
nitive impairment due to definite etiologies, such as
trauma or vascular or psychiatric diseases. Any clin-
ical subtype of MCI was considered eligible. MCI
defined by a single scale was considered insufficiently
credible and unreliable.
Types of interventions
We included supervised structured exercises of
any frequency, intensity, duration, or time directed
at improving physical fitness. Combined exercise
interventions with two or more types were included
as multimodal training; however, studies involving
exercise programs that combined cognitive training
or other non-exercise activities (e.g., diets, drugs,
and video games), not fully supervised or lasted < 4
weeks, were excluded.
Types of control groups
We included studies that involved comparators
who engaged in a strength or balance tone, a pro-
gram of social or mental activities, no treatment, or
on the waiting list.
Types of outcomes
The primary outcome was cognitive function that
was evaluated using a measurable cognitive screen-
ing instrument, whereas the secondary outcome was
the dropout rate. Studies with no outcomes in spe-
cific domains of cognitive fields or studies that
only involved the Mini-Mental State Examination
(MMSE) or Montreal Cognitive Assessment (MoCA)
were excluded. Two authors (WS and KH) initially
excluded articles that did not meet the inclusion
criteria, based on their titles and abstracts. After dedu-
plication, the remaining articles were independently
screened for eligibility by full-text assessment based
on the defined inclusion criteria. Disagreements were
1265
resolved through discussions with expert HZ (study
selection procedure, Fig. 1).
Quality assessment and data extraction
We extracted types of data from the full-text
articles, including study characteristics of author;
published year; country; RCT design, including
grouping, sample size, sex ratio, mean age, MMSE
score before the intervention, and diagnostic crite-
ria; characteristics of the exercise intervention group,
including type, intensity, frequency, duration, and
time; and outcome neuropsychological tool used for
measuring cognitive function. If the full text or data
were incomplete, the author was contacted via email.
The protocol of each included study was examined
to verify reporting bias. The quality of individual
study was assessed using the Cochrane Risk of Bias
Tool (Fig. 2) [45]. Risk was assessed to be “low,”
“high,” or “unclear.” Two independent authors (HL
and HD) assessed the risk of bias. Disagreements
were resolved by discussion with a third author.
Data synthesis and statistical analyses
Review Manager (RevMan) version 5.3 was used
for all analyses. The summary statistics required for
each assessment for continuous data were the post-
intervention mean scores, standard deviation, and
number of participants in each group (several stud-
ies did not provide change scores). The mean was
entered as negative when a higher score indicated
worse performance (e.g., reaction time, trail mak-
ing test). Cognitive function is normally assessed
using both global and individual cognitive tests.
There are general cognitive tests (MMSE, MoCA)
and specific tests that cover cognitive domains,
including memory, attention, visuospatial processing,
language, executive function, and social comport-
ment. We classified the cognitive outcomes assessed
using various neuropsychological tests into seven
domains: (1) immediate memory, (2) working mem-
ory, (3) delayed memory, (4) processing speed, (5)
attention, (6) executive function, and (7) recognition
[27]. For each domain, we included only one test from
a single trial that was used more frequently or closer
to the domain. For dichotomous data, we extracted
the number of participants in each group for each
trial. Statistical analyses were performed if more than
one study could be grouped into cognitive domains
according to intervention (e.g., aerobic or resistance
exercise). When only one study involved a category,
1266 H. Li et al. / Review of Exercise Treatment on MCI

Fig. 1. PRISMA flow diagram of the literature selection process.

Fig. 2. Cochrane’s Quality Assessment: summary of risk of bias for each quality item for each included study.
 H. Li et al. / Review of Exercise Treatment on MCI
the statistics from that single study were reported,
but not analyzed. For continuous variables measured
on different scales, standardized mean differences
(SMDs) and 95% confidence interval (CI) were cal-
culated; for dichotomous variables, risk ratios and
95% CIs were calculated.
The I2 statistic was calculated to describe the
proportion of true heterogeneity in the observed
variance across studies. Cochrane’s handbook rec-
ommends heterogeneity as not important (0–40%),
moderate heterogeneity (30–60%), substantial het-
erogeneity (50–90%), and considerable heterogene-
ity (75–100%). Sensitivity analysis was performed
when I2 was > 50% [46]. For which data were
available, meta-analyses were performed using the
inverse-variance method. A random-effects model
was used to assess the cognitive outcomes and
dropout rates. Given the small number of included
studies, we did not perform a funnel plot visual test
to investigate publication bias [9, 47].
RESULTS
Included studies
The initial database search identified 3,723 records
(PubMed, n = 886; Embase, n = 865; Cochrane,
n = 1,972) (Fig. 1). After duplicates were removed
and screened, the full texts of 286 articles were
assessed for eligibility, of which 12 met the eligibil-
ity criteria (Tables 1–3). A total of 708 participants
were included and assessed in this systematic review.
Seven trials of 122 participants assessed the treat-
ment effects of aerobic exercise, including bicycle or
motor-driven treadmill training [48–51] (n = 66) and
walking [52–54] (n = 56); six trials of 116 participants
reported on resistance exercise, including elastic band
training [55–57] (n = 48), circuit exercise [51, 53]
(n = 46), and dumbbell training group [58] (n = 22).
Moreover, one trial researched on multimodal exer-
cise [59] (n = 147). In total, 112 participants with
MCI in the control groups were compared to the aer-
obic training group, who received a waiting list, a
maintaining lifestyle routine, a strength or balance
tone, muscle-stretching exercises, or social visits; 126
participants in the control groups were compared to
the resistance training group, who received a regular
lifestyle routine, a strength or balance tone, stretching
exercises, or lecture counseling classes; and 131 par-
ticipants in the control groups were compared with
the multimodal exercise group. Three mind–body
training studies were excluded because their exercise
1267
protocol involved home-based exercise and lacked
supervision [60–62]. No further articles were found
by searching the reference lists of reviews identified
during the initial search or in the included articles.
Risk of bias
Studies without a statement of random sequence
generation or allocation concealment in sufficient
detail were judged to have an “unclear” risk of bias
[45]. Most of the studies did not report protocols;
therefore, it was not possible to determine if there
was a selection bias. In all the assessed studies, it was
not feasible to blind the participants to exercise train-
ing interventions. Therefore, the included studies all
showed “high risk” of blinding for participants and
personnel (performance bias). Half of the included
studies stated that non-blind or without details of
blinding of outcome assessors. It was judged non-
blind as a “high-risk” bias and “not clear” for that
without details of the detection bias. Studies were
assessed as having a high risk of bias for incomplete
outcome data (attrition bias) if they had a relatively
high and unbalanced missing rate between groups or
did not account for dropout. All other sectors had a
low risk of bias (Fig. 2).
Aerobic exercise intervention versus control
group
Seven studies including 234 participants with
MCI relative to aerobic exercise intervention and
any active or no intervention control groups were
pooled for meta-analyses, which contributed data
to no less than one cognitive domain [48–54]. The
grouping of cognitive scales and studies over spe-
cific domains of cognitive function is shown in
Table 4. We were able to perform meta-analyses
at all seven of our pre-specified cognitive domains
(Supplementary Material, Outcome 1.1 to Outcome
1.7). The results revealed no heterogeneity (I2 = 0%)
across studies investigating processing speed and
recognition, low heterogeneity in immediate mem-
ory (I2 = 24%), moderate heterogeneity in working
memory (I2 = 47%), delayed memory (I2 = 36%),
and attention (I2 = 42%). However, studies including
executive function demonstrated substantial het-
erogeneity (I2 = 62%). A sensitivity analysis was
performed with the main analysis performed with
and without each study in investigating execu-
tive function; the significance of the results did
not change (Supplementary Material, Outcome 1.6
and Outcome 1.6.1). The duration of each aerobic
 Table 1

1268
Characteristics of studies – aerobic exercise versus control group
Study RCT Country Group (N) Sex (male/ Mean age MMSE Diagnosis criteria Exercise Outcome
design female)
Tsai et al. [51] Parallel China Aerobic exercise 5/14 (AE) 66.00 (AE) 27.16 ± 1.26 (AE) Gauthier 2006, AE: Working memory: Digit span
(AE) n = 19 7/11 (RE) 65.44 (RE) 26.56 ± 1.34 (RE) Petersen 2004, Type: Bicycle ergometer or of Wechsler-IV Adult
Resistance 5/13 (CO) 65.17 (CO) 27.00 ± 1.65 (CO) Winblad 2004 motor-driven treadmill intelligence test
exercise (RE) Intensity: 70–75% of the target
n = 18 heart rate reserve (HRR)
Static stretching Frequency: 3 sessions/week
exercises (CO) Duration: 40 min
n = 18 Time: 16 weeks
CO:
Type: Static stretching exercises
Intensity: No load
Frequency, duration, and time:
same to AE group

H. Li et al. / Review of Exercise Treatment on MCI

Yogev-Seligmann Parallel Israel AE n = 13 8/5 (AE) 70.84 (AE) Not mentioned Albert 2011 AE: Immediate and delayed
et al. [50] Balance and tone 7/7 (BAT) 71.92 (BAT) Type: Stationary bicycles memory: The Rey Auditory
(BAT) n = 14 Intensity: 70% to 80% HRR; Verbal Learning Test
Frequency: 3 sessions/week Working memory: Digit span
Duration: 40 min component of the Wechsler
Time: 16 weeks memory test
BAT: Processing speed: The color
Type: balance, gross motor version of the trail making
coordination, and light toning test 1
exercises Execution function: The
Intensity: maintaining heart rate verbal fluency test
below 30% of HRR Attention: The color version of
Frequency, duration, and time: the trail making test 2
same to AE group Recognition: Faces/houses
recognition test
Scherder et al. Parallel America AE n = 15 2/13 (AE) 84 (AE) 9.73 ± 1.94 (AE) Petersen 1999 AE: Executive function: Retrieve
[52] Hand and face 1/14 (CO) 86 (CO) 9.87 ± 1.41 (CO) Type: Self-paced slow walking familiar information from
exercises with an aid semantic memory (Category
Control (CO) Frequency: 3 sessions/week Naming);
n = 15 Duration:30 mins Processing speed:
Time:6 weeks Trail-making A + B
CO: Working memory: Digit span
One subgroup eight subjects from the Wechsler Memory
received social visits as a Scale—Revised
‘treatment’, while in the other Memory: Visual Memory
subgroup the remaining seven Span, The Verbal Learning
subjects continued their and Memory Test, Direct
normal social activities. Recall; Rivermead
Behavioural Memory Test
(faces, pictures)
Delayed memory and
recognition: The Verbal
Learning and Memory Test,
delayed recall and
recognition.
Study RCT Country Group (N) Sex (male/ Mean age MMSE Diagnosis criteria Exercise Outcome
design female)
Nagamatsu et al. Parallel Canada AE n = 30 All female 75.6 (AE) 27.4 ± 1.5 (AE) Petersen2004 AE: Verbal memory and learning:
[53] RE n = 28 73.9 (RE) 27.0 ± 1.8 (RE) Type: Outdoor walking The Rey Auditory Verbal
BAT n = 28 75.1 (CO) 27.1 ± 1.7 (CO) Intensity: 70% to 80% of HRR, Learning Test, delayed recall;
13–15 on the RPE scale Spatial Memory: recall the
Frequency: 2 sessions/week spatial location of dots
Duration: 60 min presented on a screen;
Time: 26 weeks Processing speed: Choice
BAT: Reaction Time
Type: Stretching exercises,
range of motion exercises,
balance exercises functional
and relaxation techniques

H. Li et al. / Review of Exercise Treatment on MCI

Intensity: No loading
Duration and time: same with
RE group
Law et al. [48] Parallel China AE n = 16 8/8 77.94 (AE) Not mentioned Albert 2011 AE: Memory: Chinese Version
Waitlist control 5/9 75.14 (CO) Type: Structured whole body Verbal Learning Test;
group (CO) movement exercise, bicycle, Processing speed: Trail
n = 14 and arm ergometry Making Test A
Intensity: Moderate intensity Attention: Trail Making Test B
aerobic exercise, at 4–5/10 on
rate of perceived exertion
Frequency: 12 sessions
Duration: 60-min
Time: 8 weeks
Combourieu Parallel France AE n = 18 Not 77.1 (AE) 28.2 ± 0.43; Petersen 2004 AE: Executive function: The
Donnezan et al. Cognitive mentioned 79.2 (CO) 27.3 ± 0.5 Type: Bikes training Matrix
[49] training; Intensity: moderate intensity Reasoning test
Combined (i.e., 60% HR) Attention: The flexibility part
training; Frequency: 2 sessions/week of the Stroop Color Word test,
Control group Duration: 60 min The Digit Span Forward test
(CO) n = 14 Time: 12 weeks Working memory: The Digit
Span Backward test
Damirchi et al. Parallel Iran AE n = 11 All female 68.81 (AE) 23.18 ± 2.18; Petersen 2004 Type: Walking with muscular Processing speed: Reaction
[54] Mental training; 69.11 (CO) 23.44 ± 2.06 strength training time, Digit Symbol Coding
Exer- Intensity: Walking from 55% to test
cise + mental; 75% heart rate reserve, Attention: Modified Stroop
Control group muscle strength rating of color word test error number,
(CO) n = 9 perceived exertion within the Digit span forward subtests of
desired 13 to 15 range; the Wechsler Adult
Frequency: 3 sessions/week; Intelligence Scale
Duration: 60 min;
Time: 8 weeks

1269
 Table 2

1270
Characteristics of studies – resistance exercise versus control group
Study RCT Country Group (N) Sex (male/ Mean age MMSE Diagnosis Exercise Outcome
design female) criteria
Tsai et al. [51] Parallel China Resistance 7/11 (RE) 65.44 (RE) 26.56 ± 1.34 (RE) Gauthier 2006, RE: Working memory: Digit
exercise (RE) 5/13 (CO) 65.17 (CO) 27.00 ± 1.65 (CO) Petersen 2004, Type: Circuit-exercise use span of Wechsler-IV Adult
n = 18 Winblad 2004 free weights and intelligence test
Static stretching bodybuilding machines
exercises (CO) Intensity: 75% of their target
n = 18 1-RM
Frequency: 3 sessions/week
Duration: 40 min
Time: 16 weeks
CO:
Type: Static stretching

H. Li et al. / Review of Exercise Treatment on MCI

exercises
Intensity: No load
Frequency, duration, and
time: same to RE group
Hong et al. [55] Parallel Korea RE n = 10 3/7 (RE) Male 78.33 Not mentioned Petersen 1999 Type: Elastic band Execution function:
CO n = 12 3/9 (CO) Female 77.71 Frequency: 2 sessions/week Category/Semantic fluency
(RE) Intensity: 15-repetition test, Letter/Phonemic
Male 78.33 maximum (15RM, about fluency test;
Female 75.11 65% of maximum) Attention and working
(CO) Duration: 60 min memory: The digit span
Time: 12 weeks test; Stroop test;
CO: maintain current lifestyle Immediate Memory and
recognition: Short-term
and recognition memory,
Rey 15-Item Memory Test
Yoon et al. [57] Parallel Korea RE n = 22 6/14 (RE) 73.82 (RE) 24.23 ± 2.89 (RE) CDR, Kelaiditi RE: Memory: Rey 15-Item
CO n = 23 7/16 (CO) 74.03 (CO) 24.22 ± 1.86 (CO) 2013 Type: High-speed resistance memory test;
training Processing speed and
Intensity: blue elastic bands, attention: Trail Making
at a perceived exertion rate A&B Test, Working
of 12–13; 2–3 sets of 12–15 memory: Digit Span (both
repetitions forward and backward) test;
Frequency: 3 sessions/week Executive functions: Frontal
Duration: 60 min assessment battery
Time: 16 weeks
CO:
Type: Balance and resistance
band stretching
Frequency: 2 sessions/week
Duration and time: same with
RE group
Study RCT Country Group (N) Sex (male/ Mean age MMSE Diagnosis Exercise Outcome
design female) criteria
Nagamatsu et al. Parallel Canada Aerobic All female 75.6 (AE) 27.4 ± 1.5 (AE) Petersen 2004 Type: Keiser Pressurized Air Verbal memory and
[53] Training (AE) 73.9 (RE) 27.0 ± 1.8 (RE) system learning: The Rey
n = 30 75.1 (CO) 27.1 ± 1.7 (CO) Intensity: 6–8 repetitions Auditory Verbal Learning
RE n = 28 (two sets), 13–15 on the Test, delayed recall; Spatial
Balance and Borg’s Rating of Perceived Memory: recall the spatial
Tone (BAT) Exertion location of dots presented
n = 28 Frequency: 2 sessions/week on a screen;
Duration: 60 min Processing speed: Choice
Time: 26 weeks Reaction Time

H. Li et al. / Review of Exercise Treatment on MCI

BAT:
Type: Stretching exercises,
range of motion exercises,
balance exercises functional
and relaxation techniques
Intensity: No load
Duration and time: same with
RE group
Lee et al. [56] Parallel Korea RE n = 18 7/11 73.7 (RE) 23.8 ± 2.9; CDR Morris RE: Executive function: Frontal
Control: lecture 9/13 74.2 (CO) 23.4 ± 1.3 1993 Type: High speed elastic band Assessment Battery
consultation Frequency:3 sessions/week
(CO) n = 22 Intensity:10–12 repetitions of
two to three sets, perceived
exertion index ranging from
12 to 13
Duration: 50 min
Time: 8 weeks
Lü et al. [58] Parallel China RE n = 22 6/16 69.00 (RE) 27.23 ± 1.63; Petersen, 1999 RE: Attention: The Trail Making
CO n = 23 7/23 70.43 (CO) 26.43 ± 2.00 Type: Momentum based Test B; The Digit Span Test
dumbbell-training forward
Intensity: Each individual Working memory: The Digit
spinning exercise lasted 1–2 Span Test backward
minutes with repetitions set
at 4–5 minutes.
Frequency: 3 sessions/week
Duration: 60 min
Time:12-week

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1272 H. Li et al. / Review of Exercise Treatment on MCI

exercise intervention in these studies lasted from 30

learning delayed recall test

Episodic memory: The list
to 60 min, with 1–3 sessions/week, ranging from 6

Category verbal fluency

Memory Inventory for

Cognitive complaints:
to 26 weeks. There was no significant difference

Executive function:
between the aerobic exercise and control groups

test; Subjective
in immediate memory (p = 0.79), executive func-
tion (p = 0.1), working memory (p = 0.49), processing

Chinese
Outcome

speed (p = 0.93), delayed memory (p = 0.96), atten-

tion (p = 0.39), or recognition (p = 0.56). One study
observed the maintenance effects of aerobic exer-

Attending in social activities

cise after treatment termination, reporting that the
Frequency: 3 sessions/week
toning exercise, one mind

aerobic exercise session

treatment effects declined during the treatment-free

body exercise and one
Type: One stretching &

period [52]. There was no difference between the

Duration: 60 min
Time: 12 months

aerobic exercise and control groups in dropout rates

(odds ratio [OR], 2.47; 95% CI, 0.94–6.49; seven
trials, 251 participants; Supplementary Material,
Exercise

Outcome 1.8). Two studies reported no adverse events

AE:

S:

in any group during the course of the intervention

Characteristics of studies –Multimodal exercise versus control group

[48, 50]. One study reported the presence of adverse

Winblad 2004

events, including episodes of shortness of breath that

Diagnosis

resolved with rest and non-injurious falls [53], with

criteria

no significant differences between groups (p = 0.54).

The other studies did not mention any adverse events.
25.8 ± 2.3 (ME);

Resistance exercise intervention versus control

25.6 ± 2.4 (S)

group
Table 3

Six studies including 242 participants with MCI

MMSE

relative to resistance exercise intervention and any

active or no intervention control groups were pooled
for meta-analyses, which contributed data to at least
75.5 (ME)
Sex (male/ Mean age

one cognitive domain [51, 53, 55–58]. We performed

75.4 (S)

meta-analyses on five cognitive domains because

only one study was involved in the domain of delayed
memory [53] and recognition [55] each (Figs. 3
29/101 (S)
female)

and 4; Supplementary Material, Outcome 2.1 to

34/113
(ME)

Outcome 2.4, Outcome 2.7). The results revealed

no heterogeneity (I2 = 0%) across studies investigat-
motion exercise

ing immediate memory and executive function and

Cognitive group;

Social group (S)

(ME) n = 147;

low heterogeneity in attention (I2 = 13%); however,

cognitive-
Multimodal
Group (N)

physical

studies including working memory (I2 = 32%) and

Integrated

n = 131
Group;

processing speed (I2 = 42%) demonstrated moderate

heterogeneity.
The duration of each resistance exercise interven-
Country

China

tion in these studies lasted from 40 to 60 minutes,

with 2–3 sessions/week, ranging from 8 to 26 weeks.
Meta-analysis on pooled data revealed significant
Parallel
design

improvement differences for the resistance exer-

RCT

cise intervention versus control groups on measures

of attention (0.48 [0.06–0.89], p < 0.05) and exec-
Lam et al. [59]

utive function (0.44 [0.05–0.83], p < 0.05), but not

on immediate memory (p = 0.79), working memory
(p = 0.19), processing speed (p = 0.92), delayed mem-
Study

ory (p = 0.82), or recognition (p = 0.77). There was

 H. Li et al. / Review of Exercise Treatment on MCI 1273

Table 4
Grouping of cognitive tests and studies over cognitive functions
Cognitive function Cognitive tests Trial
Immediate memory The Verbal Learning and Memory Test Direct recall Scherder et al. [52]
Chinese Version Verbal Learning Test, total free recall Law et al. [48]
The Rey Auditory Verbal Learning Test Nagamatsu et al. [53], Yogev-Seligmann et al. [50]
Rey 15-Item Memory Test Hong et al. [55], Yoon et al. [57]
Working memory Digit span backward Lu et al. [58], Combourieu Donnezan et al. [49], Hong
et al. [55]
Digit span component of the Wechsler memory test Scherder et al. [52], Yoon et al. [57], Tsai et al. [51],
Yogev-Seligmann et al. [50]
Delayed memory Rey auditory verbal learning test delayed recall trail Nagamatsu et al. [53], Yogev-Seligmann et al. [50]
The Verbal Learning and Memory Test, delayed recall Scherder et al. [52]
Chinese Version Verbal Learning Test, delayed recall Law et al. [48]
The list learning delayed recall test Lam et al. [59]
Processing speed Reaction time of modified Stroop color-word test Damirchi et al. [54]
Reaction time of spatial memory Nagamatsu et al. [53]
Trail making test A Yoon et al. [57], Law et al. [48], Yogev-Seligmann et al.
[50]
Trail-making A + B Scherder et al. [52]
Attention Trail making test B Lu et al. [58], Yoon et al. [57], Law et al. [48],
Yogev-Seligmann et al. [50]
Digit span (forward) Combourieu Donnezan et al. [49], Damirchi et al. [54],
Hong et al. [55]
Executive function Category verbal fluency Scherder et al. [52], Lam et al. [59]
Verbal fluency, semantic Hong et al. [55], Yogev-Seligmann et al. [50]
Frontal Assessment Battery Yoon et al. [57], Lee et al. [56]
Matrix Reasoning test Combourieu Donnezan et al. [49]
Recognition Faces/houses recognition Yogev-Seligmann et al. [50]
The Verbal Learning and Memory Test, recognition Scherder et al. [52]
Rey 15-Item Memory Test, recognition Hong et al. [55]

Fig. 3. Outcome 2.5 Impact of resistance exercise training on attention. CI, confidence interval; IV, inverse variance; SD standard deviation;
Std, standardized.

no difference in the dropout rates between the resis-
tance exercise and control groups (OR, 1.21; 95%
CI, 0.59–2.50; six trials; Supplementary Material,
Outcome 2.8). One study reported the maintenance
effects of resistance exercise treatment on partici-
pants with MCI [49], and the outcome of the matrix
reasoning test (p < 0.01) and digit span forward
(p < 0.05) still improved for the 6-month post-test
relative to the pre-test. Two studies reported no
adverse events in any group during the course of the
intervention [56, 58]. One study reported no signifi-
cant differences of adverse event occurrence between
groups (p = 0.54) [53]. The other studies did not men-
tion any adverse events.
Multimodal exercise intervention versus control
group
Lam et al. assessed the effect of multimodal
exercise intervention on cognitive function in 114
individuals with MCI [59]. These cognitive domains
1274 H. Li et al. / Review of Exercise Treatment on MCI
Fig. 4. Outcome 2.6 Impact of resistance exercise training on executive function. CI, confidence interval; IV, inverse variance; SD standard
deviation; Std, standardized.
involved outcomes of pre- and post-training measures
of delayed recall and executive function (category
verbal fluency test). The trial had a fair method-
ological quality. The author found a significant
improvement favoring multimodal exercise interven-
tion over the control group on measures of both
the category verbal fluency test and delayed recall
after 12 months of intervention (multilevel model,
p < 0.001). There was no difference between the mul-
timodal exercise and control groups in the dropout
rates. This study reported no adverse events associ-
ated with this intervention. No differences in age and
educational level were observed between completers
and defaulters.
DISCUSSION
Summary of main results
We examined the effects of aerobic, resistance, and
multimodal exercise training on cognitive function in
adults aged > 60 years with MCI. One multimodal
exercise intervention study was presented insuffi-
ciently. Meta-analysis results revealed that, compared
to the control group, resistance exercise significantly
improved performance on measures of attention and
executive function. No significant differences were
observed in any of the remaining cognitive domains.
We included 12 studies after screening because
of a more qualified inclusion criterion. Most stud-
ies involved small sample sizes. There was significant
heterogeneity in the methodologies across the studies
involved, including sample size, exercise schemes,
participant compliance, and study quality. Although
the review analyzed the fine-sorted subgroups of cog-
nitive function, there could be variations in the results
of each measure. We observed that half of the stud-
ies reported significant improvements in composite
measures of cognitive function for exercise versus
controls, including executive function [49, 52, 57],
working memory [55], and processing speed [50,
52, 53, 57]. Despite this, the majority of compar-
isons yielded no significant differences. Additionally,
the results of this meta-analysis could have been
affected by the quality of the included trials. Across
the included papers, approximately half did not state
the methods of randomization or blinding of outcome
assessors. For all but one trial, allocation was poorly
reported. No trial evaluated contamination bias that
could have interfered with the outcomes. Only two tri-
als reported protocols [57, 59]; for most trials, it was
not feasible to determine whether there was selective
reporting of results.
Some researchers have suggested that improve-
ments in cognitive function could be attributed to
improvements in cardiovascular fitness due to exer-
cise [63]. Changes in grip strength and walking
speed have been correlated with mental state and
fluid cognition [64]. However, most trials involved
in this review did not report any objective measures
of cardiorespiratory fitness. In addition, studies have
reported that short session duration and higher fre-
quency might predict higher effect sizes [65, 66].
However, owing to the inconsistency of exercise
modalities in this review, dose-response tests were
not performed in this study.
Agreements and disagreements with other studies
or reviews
Seven meta-analyses published data based on sim-
ilar hypotheses yet failed to find comparable results.
 H. Li et al. / Review of Exercise Treatment on MCI
Gates et al. assessed the effects of exercise on
cognitive function in 14 RCT trials with 1,695 par-
ticipants [43]. Their eligibility criteria differed from
this study in that they included participants with
probable MCI, and subjective memory decline who
were aged > 65. We both set the criteria for exercise
intervention up longer than 4 weeks and prescribed
them specifically. However, we only included trials
that reported exercise training effectively supervised
by centers, physicians, or professionals; those self-
reported, at home, or without reported supervision
were excluded. The authors concluded that there is
limited evidence to prove that any exercise modality
improves cognitive function in individuals with MCI.
De Souto Barreto et al. reviewed five papers on
long-term exercise (12 months or longer) in older
adults with MCI, onset of dementia, or clinically
meaningful cognitive decline [67]. Apart from the
inclusion criteria, another difference is that they con-
sidered the change in MMSE score as a main outcome
indicator and analyzed the overall effect of exercise,
whereas we discussed the different exercise modali-
ties separately. Their review observed no significant
effects of exercise, either individually or in combina-
tion, on reducing the risk of cognitive decline.
Zhang et al. published a meta-analytic review
of traditional Chinese exercise in older adults with
MCI [68]. They found that four Tai Chi studies and
one Liuzijue study met the inclusion criteria. We
excluded trials on participants with MCI with a def-
inite etiology, whereas this review included medical
or neurological disorders, such as AD, dementia,
or Parkinson’s disease. The authors concluded that
exercise improved the visuospatial function for indi-
viduals with MCI.
The meta-analysis presented by Lee et al. has a
similar aim (reporting the effects of exercise interven-
tion for older adults with MCI) and exclusion criteria
(cross-sectional, protocol, and review studies) [69].
In contrast to this review, our study subdivided cog-
nitive function into detailed items instead of MMSE.
In addition, this review finally involved three eligible
studies, including five exercise interventions (aerobic
or resistance exercise) combined for data analysis,
and only one study was classified into a functional
category. This review reported that cognitive function
was significantly increased in the exercise group.
Biazus-Sehn et al. reviewed the global effects of
various exercise modalities on MCI. Their search
identified 27 studies that reported data [42]. The dif-
ference is that they involved participants with a mean
age of ≥60 years who had other diseases, such as
1275
insulin resistance. We excluded those who were not
purely cognitively impaired but had other diseases,
which might disturb the exercise effect and cognitive
function. They reported improved global cognitive
function, executive function, and delayed recall after
the exercise.
Similarly, Zhu et al. reviewed and analyzed aerobic
dance in participants with MCI aged > 50 years. This
meta-analysis involved five studies with 842 patients
[70]. They found that aerobic dance, including Tai
Chi, improved global cognitive function and memory
executive function in older adults with MCI.
A meta-analysis by Lin et al. assessed the effects of
Tai Chi on cognitive performance. Except for exercise
intervention, the criteria differed from this review in
including younger participants with MCI [71]. This
meta-analysis indicated that Tai Chi has positive clin-
ical effects on cognitive function (global cognitive
function, memory and learning, executive function)
in older adults with MCI.
Implications for practice and research
We found that resistance exercise improved exec-
utive function and attention performance in patients
aged > 60 years. However, there might be some con-
founding factors in the outcomes. First, there are
more studies and diversified scales involved in aer-
obic exercise analyses, which might lead to higher
heterogeneity, and the large variability in training
paradigms and study quality might also influence the
outcome. Further investigations into the parameters
and populations most associated with the efficacy of
physical training for cognitive function are neces-
sary. Cognition is a complex and multi-class function;
however, there is insufficient evidence to illustrate the
relationship between exercise and brain-processed
cognitive function. Certainly, clear differences exist
in the effects of exercise on the cognition subgroups.
Within the seven disparate intrinsic connectivity net-
works in the brain, the beneficial effects exerted by
aerobic exercise might be mediated by the greatest
association with the executive and dorsal attention
networks [72]. Exercise activates the hub region of
the executive network (e.g., attention, working mem-
ory, cognitive control) in the brain [11, 73], and the
duration of exercise may be positively correlated with
its volume [74]. Exercise-induced brain functional
homogeneity variation is likely to improve executive
control behavior and predict attention behavior [75].
This evidence may help to explain the results. Thus,
to elucidate the exact relationship between exercise
1276 H. Li et al. / Review of Exercise Treatment on MCI
and cognitive function in patients with MCI, more
large-sample RCTs and animal studies are required
in the future. It also raises our wider understanding
of how to improve exercise compliance and to use a
smaller battery of cognitive scales for the uniformity
and comparability of results.
ACKNOWLEDGMENTS
This work was supported by grants from the Cap-
ital Health Research and Development of Special
(No.2020-1-6011) to HZ. We thank the authors who
provided the original article and information during
the screening and analysis.
Authors’ disclosures available online (https://
www.j-alz.com/manuscript-disclosures/22-0243r2).
SUPPLEMENTARY MATERIAL
The supplementary material is available in the
electronic version of this article: https://dx.doi.org/
10.3233/JAD-220243.
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